During the past year, we have examined the interaction of the gonadal peptide, inhibin, with the gonadal steroids as they modulate the basic brain-pituitary regulation of gonadotropin (LH and FSH) secretion. We found that inhibin can be demonstrated to suppress basal FSH secretion and all parameters of LH secretion in the intact, adult female rat but cannot be demonstrated to affect gonadotropin secretion in the intact, adult male rat. Destruction of testis Leydig cells with the selective toxicant, ethane dimethane sulfonate (EDS), revealed that Leydig cell influences, which include testosterone, can account for the total suppressive influence of the testes on all parameters of LH secretion. The Leydig cell influences suppress only basal FSH secretion, however, and only partially account for the total FSH-suppressing influence of the testes. In contrast to the intact rat, inhibin was demonstrated to account for the remaining suppressive influence of the EDS-treated testis on basal FSH secretion suggesting that the contribution of inhibin in the adult male rat is either masked by the larger Leydig cell influence or absent until activated by Leydig cell impairment. In concomitant studies, an effect of endogenous inhibin was also demonstrated in LHRH driven, juvenile male rhesus monkeys. Studies in the female rat have confirmed our previous findings that inhibin selectively suppresses only basal FSH secretion and demonstrated that pulsatile FSH secretion may be suppressed by estradiol. In addition, we have initiated in vitro studies examining pituitaries from rats in which the gonadal factors have been selectively neutralized in order to determine the affected gonadotropin secretion phase and intracellular messenger systems. Finally, we have initiated studies to characterize the different molecular weight species of inhibin and to relate the changing ratios of these forms with alterations in the reproductive state. The results from these and ongoing studies are dissecting the mechanisms by which the brain and gonads interact to control gonadotropin secretion and reproductive function.